Hypertonic saline solution (HTS) (7.5 percent sodium chloride [NaCl]) treatment (5 milliliters per kilogram) of rats subjected to uncontrolled hemorrhagic shock (n = 7) caused an initial partial recovery of blood pressure (+38 +/- 5 percent, p<0.05) and cardiac index (+48 +/- 6 percent, p<0.01) followed by increased bleeding (+53 +/- 5 percent versus rats treated with 0.9 percent NaCl, p<0.05), secondary shock (mean arterial pressure [MAP] 23 +/- 7 millimeters of mercury, p<0.01) and decreased survival (-54 +/- 15 minutes versus control, p<0.05). The increased blood loss resulted from: 1, increased vascular pressure and vasodilatation (total peripheral resistance index -27 +/- 5 percent, p<0.05), as initial bleeding occurred when MAP and cardiac index are increased compared with the control group (+88 +/- 10 percent, p<0.05 and +82 +/- 7 percent, p<0.01, respectively) and as the concomitant infusion of angiotensin II, a potent vasoconstrictor, delayed the HTS-induced bleeding (resumed at 60 minutes), and 2, a defect in platelet aggregation reflected by decreased adenosine diphosphate (ADP)-induced maximal aggregation (-79 percent versus rats treated with 0.9 percent NaCl, p<0.05) and increased EC50 of ADP (+159 percent, p<0.05). These hemodynamic and hematologic responses might be mediated at least in part by prostacyclin, a vasodilator and antiplatelet aggregator, as HTS-treated rats markedly elevated the 6-keto-PGF1 alpha per thromboxane B2 ratio (+140 +/- 12 percent, p<0.01) and pretreatment with indomethacin decreased blood loss and improved MAP and survival. These data point out potential untoward hemodynamic and hematologic consequences of HTS treatment in traumatic injury in which control of bleeding cannot be confirmed.